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LUNESTA (ESZOPICLONE): DRUG INTERACTIONS
An additive effect on psychomotor performance was seen with coadministration of Eszopiclone (Lunesta) and ethanol 0.70 g/kg for up to 4 hours after ethanol administration.
Coadministration of single doses of Lunesta (Eszopiclone) 3 mg and paroxetine 20 mg daily for 7 days produced no pharmacokinetic or pharmacodynamic interaction.
Coadministration of single doses of Eszopiclone 3 mg and lorazepam 2 mg did not have clinically relevant effects on the pharmacodynamics or pharmacokinetics of either drug.
Coadministration of Lunesta 3 mg and olanzapine 10 mg produced a decrease in DSST scores. The interaction was pharmacodynamic; there was no alteration in the pharmacokinetics of either drug.
Drugs That Inhibit CYP3A4
CYP3A4 is a major metabolic pathway for elimination of Lunesta (Eszopiclone). The AUC of eszopiclone was increased 2.2-fold by coadministration of ketoconazole, a potent inhibitor of CYP3A4, 400 mg daily for 5 days. Cmax and t1/2 were increased 1.4-fold and 1.3-fold, respectively. Other strong inhibitors of CYP3A4 (e.g., clarithromycin, itraconazole, nefazodone, ritonavir, troleandomycin, nelfinavir) would be expected to behave similarly.
Drugs That Induce CYP3A4
Racemic zopiclone exposure was decreased 80% by concomitant use of rifampicin, a potent inducer of CYP3A4. A similar effect would be expected with Eszopiclone (Lunesta) tablets.
Drugs Highly Bound to Plasma Protein
Eszopiclone (Lunesta) is not highly bound to plasma proteins (52-59% bound); therefore, the disposition of eszopiclone is not expected to be sensitive to alterations in protein binding. Administration of eszopiclone 3 mg to a patient taking another drug that is highly proteinbound would not be expected to cause an alteration in the free concentration of either drug.
Drugs with a Narrow Therapeutic Index
A single dose of eszopiclone 3 mg did not affect the pharmacokinetics of digoxin measured at steady state following dosing of 0.5 mg twice daily for one day and 0.25 mg daily for the next 6 days.
Lunesta (Eszopiclone) tablets 3 mg administered daily for 5 days did not affect the pharmacokinetics of (R)- or (S)-warfarin, nor were there any changes in the pharmacodynamic profile (prothrombin time) following a single 25 mg oral dose of warfarin.
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